Tobacco dependence is the most common substance abuse disorder and the leading preventable cause of death in the United States. More than three million lives a year worldwide are lost due to smoking. Alterations in neurocognitive function play a major role in nicotine use and addiction and have a significant impact on treatment efficacy and rehabilitation. Diminished neurocognitive function, perhaps associated with underlying comorbidity, may lead to nicotine (and similar drug) use and prevent successful smoking cessation. A better understanding of the neurocognitive dysfunctions that put individuals at risk for drug use and the alterations in neurocognitive function that occur during withdrawal and rehabilitation could significantly improve treatment outcomes. The primary goal of the proposed Phase I research is to apply an innovative neurocognitive assessment method, the alertness and memory profiler (AMP) to evaluate 26 smokers following nicotine administration and nicotine deprivation. The AMP results will be evaluated in comparison to data previously acquired from healthy subjects and patients with sleep disorders. The AMP system uniquely integrates neurophysiological, neuropsychological, behavioral and subjective measures into an easy-to-administer, 2-hour protocol. The AMP is being designed to provide a comprehensive neurocognitive assessment method with applications in neurology, psychiatry, epidemiology and sleep medicine for diagnosis and to evaluate the efficacy of pharmaceutical and other interventions. Nicotine was selected as the first drug to be evaluated with the AMP for several reasons: 1) the high prevalence of use and addiction, 2) the breadth and depth of existing research on nicotine and cognition, 3) the future potential for therapeutic applications of nicotine and nicotine agonists, and 4) the investigators observations that smoking was more prevalent among patients with untreated sleep disorders. Plans for the Phase II proposal include nicotine dose-response studies and investigations of additional drugs, specifically alcohol, caffeine and modafanil (a novel psychostimulant currently used in sleep medicine). The subject populations will be expanded to include non-smokers and patients with sleep-disorders. [unreadable] [unreadable]